Human ets genes are located on chromosome regions of interest to human cancer, as well as to human genetics. These regions are the 11q23-24 for ets-1 and 21q22.3 for ets-2. Cancer-specific chromosome abnormalities involving these regions are found mainly in leukemias, lymphomas and solid tumors (Ewing's sarcoma). Using panels of somatic cell hybrids, we have localized the ets genes relative to a number of chromosome breakpoints characteristic of specific translocations occurring in neoplastic cells. We have found the ets-1 gene locates in a very narrow region of chromosome 11, between the breakpoint of the t(4;11)(q21;q23) of an acute leukemia and the t(11;22)(q24;q12) of a Ewing's sarcoma. The ets-2 gene on chromosome 21 is bracketed by the breakpoints of a t(8;21)(q22;q22) of an acute myelogenous leukemia (AML-M2) and a t(21;22)(q22;q11) of a chronic myeloid leukemia. Both ets-1 and ets-2 were not found to be rearranged, using probes representing the 3' regions of the genes, regardless if the genes were transposed or not. Therefore, it remains to be defined whether these genes are directly involved in some of the breakpoints, or if they are in close proximity to the newly formed chimeric junctions. The ets-2 gene maps in the particular region of chromosome 21 that, when trisomic, confers the Down's syndrome (DS) phenotype. Restriction fragment length polymorphisms (RFLPs) for the ets-2 gene (Msp I and Taq I) have been used for a genetic population study aimed at the prevention of this syndrome. DS individuals, with an extra copy of chromosome 21, develop an Alzheimer-like disease. One form of Alzheimer's disease seems to have an autosomal dominant inheritance, strongly suggesting the involvement of a responsible gene on chromosome 21. This fact provides a rationale for using ets-2 RFLPs in searching for the Alzheimer's disease gene in high-risk families.